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A Role for B Cells to Transmit Hepatitis C Virus Infection
Isabelle Desombere1, Freya Van Houtte1, Ali Farhoudi1
1Department of Diagnostic Sciences, Ghent University, Ghent, Belgium.
Insights
Hepatitis C virus (HCV) can be transmitted by B cells from chronically infected patients, but not from recently infected ones. This finding has implications for developing new Hepatitis C virus vaccines.
Area of Science:
- Virology
- Immunology
- Hepatology
Background:
- Hepatitis C virus (HCV) exhibits high variability and establishes chronic infections in most patients via blood transmission.
- Limited in vitro cell culture systems hinder understanding of clinical HCV strain infectivity.
- HCV's association with and infection of immune cells may facilitate immune evasion.
Purpose of the Study:
- To investigate the role of B cells in Hepatitis C virus transmission.
- To assess the infectivity of B cells and sera from recent and chronic HCV patients in humanized liver chimeric mice.
Main Methods:
- Humanized liver chimeric mice were inoculated with B cells and sera from HCV patients.
- Infectivity was assessed by the ability of these biological materials to transmit HCV.
- Association between anti-glycoprotein E1E2 antibodies and B cell transmission was evaluated.
Main Results:
- B cells from chronically infected patients transmitted HCV, while their sera did not.
- B cells from recently infected patients did not transmit HCV, but their sera were infectious.
- Circulating anti-glycoprotein E1E2 antibodies correlated with B cell-mediated HCV transmission.
Conclusions:
- B cells play a significant role in Hepatitis C virus transmission, particularly in chronic infections.
- These findings suggest B cells as a potential target for HCV therapies and vaccines.
- The study highlights the importance of considering B cell involvement in HCV pathogenesis and vaccine design.
Abstract:
Hepatitis C virus (HCV) is highly variable and transmits through infected blood to establish a chronic liver infection in the majority of patients. Our knowledge on the infectivity of clinical HCV strains is hampered by the lack of in vitro cell culture systems that support efficient viral replication. We and others have reported that HCV can associate with and infect immune cells and may thereby evade host immune surveillance and elimination. To evaluate whether B cells play a role in HCV transmission, we assessed the ability of B cells and sera from recent (<2 years) or chronic (≥ 2 years) HCV patients to infect humanized liver chimeric mice. HCV was transmitted by B cells from chronic infected patients whereas the sera were non-infectious. In contrast, B cells from recently infected patients failed to transmit HCV to the mice, whereas all serum samples were infectious. We observed an association between circulating anti-glycoprotein E1E2 antibodies and B cell HCV transmission. Taken together, our studies provide evidence for HCV transmission by B cells, findings that have clinical implications for prophylactic and therapeutic antibody-based vaccine design.
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